PROTEIN LIPID INTERACTION

本建议的目的是研究几个定义明确的系统， 蛋白质和脂质相互作用。 这种相互作用对于 生物膜的组装和功能。 这些系统是：i） 细菌酶环丙烷脂肪酸合酶的作用，ii） 含脂质噬菌体PR 4的形态发生，和iii）分离 酵母突变体，酿酒酵母，缺乏 磷脂交换蛋白。 环丙烷脂肪酸合成酶是 已知仅与非极性部分特异性反应的离散酶 磷脂双分子层。 我们建议准备大量的这种 酶的重组DNA技术，并研究其详细的相互作用 与其磷脂底物结合。 噬菌体PR4从以下细胞获得其衣壳脂质： 细菌膜和这个过程似乎是一个很好的研究模型 膜形态发生通过遗传手段。 我们建议使用一种组合 基因和生物化学来研究噬菌体 脂质被掺入。 脂质交换蛋白在自然界中普遍存在 并且许多哺乳动物蛋白质已经被纯化和研究。 然而，这些蛋白质的功能尚不清楚。 S. cereviseae有这样的 蛋白质，是典型的真核生物，具有复杂的遗传系统。 我们建议利用这一遗传系统分离突变体， 这些蛋白质。 这种突变体将允许推断这些基因的作用。 真核细胞中的蛋白质。 生物的正常功能和形成 细胞膜对于细胞的生存力是必不可少的。 这些项目应提供 膜形态发生机制方面急需的信息， 功能 大量的疾病过程与缺陷有关 在膜形态发生中。

The aim of this proposal is to study several well-defined systems in which proteins and lipids interact. Such interaction are essential to the assembly and function of biological membranes. The systems are i) the action of the bacterial enzyme cyclopropane fatty acid synthase, ii) morphogenesis of the lipid-containing bacteriophage PR4, and iii) isolation of mutants of the yeast, Saccharomyces cereviseae, deficient in phospholipid exchange proteins. Cyclopropane fatty acid synthase is the only discrete enzyme known to specifically react with the nonpolar portion of a phospholipid bilayer. We propose to prepare large quantities of this enzyme by recombinant DNA techniques and to study its detailed interaction with its phospholipid substrate. Phage PR4 acquires its capsid lipid from the bacterial membrane and this process seems a good model to study membrane morphogenesis by genetic means. We propose to use a combination of genetics and biochemistry to study the mechanisms whereby the phage lipids are incorporated. Lipid exchange proteins are ubiquitous in nature and a number of mammalian proteins have been purified and studied. However, the function of these proteins is unknown. S. cereviseae has such proteins, is a typical eucaryote, and has a sophisticated genetic system. We propose to exploit this genetic system to isolate mutants difficient in these proteins. Such mutants will allow deduction of the role of these proteins in eucaryotic cells. Proper function and formation of biological membranes is essential for cell viability. These projects should provide much needed information on the mechanism of membrane morphogenesis and function. A large number of disease processes are associated with defects in membrane morphogenesis.